Collagen is the main component for maintaining the elasticity of the skin and muscle. Animal collagen that is currently known can be classified approximately into 21 types. Different kinds of collagen exist in different tissues. Out of all collagen in the skin, Type I collagen is the most abundant and has the most functions. Type I collagen accounts for about 80% of the skin collagen, and Type III collagen accounts for about 20% of the skin collagen. Fibroblasts in the dermis mainly produce Type I collagen and Type III collagen for the skin.
The layers of the skin from top to bottom are the epidermis, dermis, and hypodermis. Natural human aging processes include skin flaccidity, wrinkle formation and skin darkening, which gradually appear with aging. The causes of skin aging can be classified into endogenous and exogenous factors. Endogenous aging is a natural aging process of the human body caused by increasing age, decreasing hormone levels, and a weakened immunity. Exogenous aging is caused by extrinsic factors, such as sunshine, pollution, free radical damage, and smoking.
In general, all of the causes of endogenous and exogenous aging can promote the phosphorylation of the MAPK pathway, thereby, increasing the content of MMP in the dermis. MMP may decompose collagen and reduce the content of the collagen in the skin. Without the support of collagen, the skin becomes flaccid and the stratum corneum thickens, leading to darkened and wrinkled skin. In addition, reactive oxygen species (ROS) in cells, such as the organic and inorganic substances of superoxide anions, peroxides and free radicals may also cause the denaturation of collagen and the loss of function of collagen.
Another characteristic of skin aging is the accumulation of melanin in the skin, which causes darkened skin and/or dark spots. Melanin is produced by the basal melanocytes presented in the bottom layer of the epidermis of the skin. The melanogenesis is initiated by the binding of α-melanocyte stimulating hormone (α-MSH) secreted by the keratinocytes in the skin to melanocortin 1 receptor (MC1R) on melanocytes, to activate the cAMP pathway in the melanocytes. The tyrosinase in the melanocytes then activates and catalyzes the conversion of tyrosine to dopaquinone. Dopaquinone can be further converted to melanin through a series of biochemical reactions under the catalysis of tyrosinase related protein-1 (TRP-1) and tyrosinase related protein-2 (TRP-2).
Among all causes of skin aging, UV rays from the sun are the most damaging and significantly accelerate skin aging. Depending on the wavelength, UV rays can be classified into long wavelength UV (UVA) with a wavelength ranging from 320 nm to 400 nm, medium wavelength UV (UVB) with a wavelength ranging from 275 nm to 320 nm, and short wavelength UV (UVC) with a wavelength ranging from 200 nm to 275 nm. The primary UV rays that people are exposed to in daily life are UVA and UVB. Long term exposure of UVA and UVB may cause erythema, sunburns, damage to the deoxyribonucleic acid (DNA) in skin cells, abnormality of the skin immune system, and skin cancer.
The aging phenomenon caused by UV rays is called as “photo-aging,” which may promote the production of ROS and activate the MAPK pathway in cells, thereby increasing the content of MMPs, and leading to the decomposition of the collagen in the skin. In addition, UV rays irradiation may promote the melanogenesis of melanocytes, which causes the accumulation of melanin in the skin. Therefore, if the UV rays which the skin is exposed to can be blocked (such as by absorbing the UV rays which irradiate the epidermis of the skin, thereby, reducing the UV rays which penetrate the epidermis of the skin), the MAPK pathway in the cells can be inhibited, the activity and/or expression of MMPs can be inhibited, and/or the melanogenesis can be inhibited, the effects of improving/caring for skin quality and anti-skin aging can be achieved.
Previous studies found that ziyuglycoside-I extracted from the root of Sanguisorba officinalis by 70% ethanol can inhibit the expression of MMP-1. In addition, sumaflavone and amentoflavone extracted from Selaginella tamariscina by methanol can inhibit the expression of MMP-1. However, there is still a great need for a component which can inhibit the activity of MMPs and has a better effect of anti-aging.
The inventors of the present invention found that the compound of formula (I) of the present invention has excellent effects of anti-oxidation, inhibiting the activity and/or expression of MMPs, inhibiting the phosphorylation of mitogen-activated protein kinases (MAPKs), promoting the expression of collagen, inhibiting the activity and/or expression of tyrosinase, inhibiting the expression of tyrosinase related protein-1 and/or tyrosinase related protein-2, and/or absorbing UV rays with a wavelength ranging from 210 nm to 400 nm, so as to alleviate/prevent the decomposition and/or denaturation of collagen and inhibit melanogenesis, and thus, can be used for anti-skin aging.